Low back pain (LBP) is a complex condition that affects 65-85% of the population, and is the leading musculoskeletal condition contributing to disability in the United States. Disc herniation injuries are the most common injury and 75% of individuals undergoing surgical and rehabilitative interventions for this condition experience suboptimal or poor outcomes. These patients demonstrate disability and deficits in functional capacity, including strength and endurance of the lumbar musculature. Muscle-specific changes in individuals with LBP include altered muscle volume, fatty infiltration and fibrosis, and fiber area and type. Importantly, these changes are insensitive to rehabilitation in patients with continued chronic or recurrent symptoms. While normal disuse-related atrophy in the presence of LBP is expected, more severe or chronic pathology, such as inflammation and fiber damage, may be inducing irreversible fiber degeneration and fatty/fibrotic tissue changes that impair muscle function and recovery. While the structural and adaptive capacities of healthy muscle are well understood, muscle recovery in the presence of pathology is less clear. To address this gap in knowledge, the purpose of this proposal is to compare structural, physiological, and adaptive responses of muscle in the presence of acute and chronic lumbar spine pathology. Our central hypothesis is that chronic injury results in a state of muscle inflammation, atrophy, fibrosis, and muscle degeneration that is not responsive to exercise. Specific Aim 1 will use MRI and direct tissue measurements to compare macro and microscopic structural properties of multifidus muscles in patients with acute versus chronic lumbar disc injury. Specific Aim 2 will compare the passive mechanical and load-bearing protein changes in the multifidus of patients with acute versus chronic lumbar disc injury to identify the mechanism of increased muscle stiffness. Following a defined bout of pre-operative exercise, Specific Aim 3 will identify which patients respond to exercise by examining muscle hypertrophic, fibrotic, inflammatory, and adipogenic gene expression profiles. These patients will be followed for six months post-operatively to measure muscle recovery and strength. These experiments will elucidate the structural, mechanical, and adaptive potential of lumbar spine muscles in these patients. This contribution is significant because it is the first step in a precision medicine approach aimed at reversing atrophic or degenerative muscle changes that obstruct patient recovery. The proposal is innovative because it utilizes novel direct tissue testing and MRI methods to measure muscle structure, function, and adaptation in living humans. We expect an immediate impact on rehabilitation because these findings will provide evidence and methods for identifying patients who will or will not respond to standard rehabilitation programs. In the long-term, we expect these experiments will provide direction for unique, patient-specific pharmacological, surgical and rehabilitation programs.